雷帕霉素预处理对大鼠肢体缺血-再灌注诱发肺损伤的影响  

Effects of rapamycin preconditioning on lung injury induced by limb ischemia-reperfusion in rats

作　　者：黄丹[1] 肖凡[1] 郑小兰[1] 罗振中[1] 徐国海[1] 唐斌[2] 

机构地区：[1]南昌大学第二附属医院麻醉科,330006 [2]江西省人民医院急诊科

出　　处：《临床麻醉学杂志》2017年第7期693-696,共4页Journal of Clinical Anesthesiology

基　　金：江西省卫生计生委科技计划(20165283)

摘　　要：目的探讨雷帕霉素预处理对大鼠肢体缺血-再灌注诱发肺损伤的影响及相关机制。方法健康雄性SD大鼠60只,4~5月龄,体重250~300g,采用随机数字表法分为五组:假手术组(S组)、肢体缺血-再灌注组(IR组)、雷帕霉素1、5、10mg/kg预处理组(R1、R5和R10组),每组12只。采用肢体缺血2h再灌注3h的方法制备肢体缺血-再灌注损伤模型。检测各组血清超氧化物歧化酶(SOD)活性、丙二醛(MDA)、IL-1β、IL-6和TNF-α的浓度;取肺组织,光镜下观察肺组织病理学结果,并测定肺组织湿干比重(W/D)。结果 IR、R1和R5组SOD活性明显低于S组(P<0.05);R1、R5和R10组SOD活性明显高于IR组,且R5和R10组明显高于R1组,R10组明显高于R5组(P<0.05)。IR、R1和R5组血清MDA、IL-1β、IL-6、TNF-α浓度和肺W/D明显升高(P<0.05);R1、R5和R10组血清MDA、IL-1β、IL-6、TNF-α浓度和肺W/D明显降低,且R5和R10组明显低于R1组,R10组明显低于R5组(P<0.05)。与S组比较,IR组肺组织病理学损伤加重;与IR组比较,R1、R5和R10组肺组织病理学损伤逐渐减轻。结论雷帕霉素预处理可减轻大鼠肢体缺血-再灌注诱发的肺损伤,并且呈剂量依赖性,剂量越大,其减轻肢体缺血-再灌注诱发肺损伤的作用越强,其机制可能与抗氧化应激和抗炎反应有关。Objective To discuss the effects and related mechanisms of rapamycin preconditioning on lung injury induced by limb ischemia-reperfusion（IR）in rats.Methods Sixty healthy male SD rats,aged 4-5months,weighing 250-300 g,were randomly divided into 5groups（n=12each）using a random number table：sham operation group（group S）;limb ischemia-reperfusion group（group IR）;rapamycin 1,5,10mg/kg pretreatment groups（groups R1,R5 and R10）.Ischemia-reperfusion of limb was produced by occlusion of bilateral femoral arteries for 2h followed by 3hreperfusion.Blood samples were collected to determine serum superoxide dismutase（SOD）,malondialdehyde（MDA）,interleukin-1β（IL-1β）,interleukin-6（IL-6）and tumor necrosis factor-α（TNF-α）concentrations,1ungs were removed for microscopic examination and for determination of wet/dry lung weight ratio.Results The activity of SOD in groups IR,R1 and R5was significantly lower than that in group S（P〈0.05）.The activity of SOD in groups R1,R5 and R10 was significantly higher than that in group IR,that in groups R5 and R10was significantly higher than that in group R1,that in group R10 was significantly higher than that in the group R5（P〈0.05）.Serum MDA,IL-1β,IL-6,TNF-αconcentrations and wet/dry lung weight ratio were significantly increased in groups IR,R1 and R5（P〈0.05）.Serum MDA,IL-1β,IL-6,TNF-αconcentrations and wet/dry lung weight ratio were lower in groups R1,R5 and R10,those in groups R5 and R10were significantly lower than those in group R1,those in group R10 was significantly lower than those in group R5（P〈0.05）.Compared with group S,the lung tissue injured more significantly in group IR.Compared with group IR,the lung tissue injury gradually reduced in groups R1,R5 and R10.Conclusion Rapamycin pretreatment can reduce lung injury caused by limb ischemia-reperfusion injury in rats in a dose-dependent manner,the greater the dose,the stronger the effect of reducing lung injury caused by limb ischemia-reperfusion injury.The mech

关 键 词：雷帕霉素 再灌注损伤 呼吸窘迫综合征 预处理 SD大鼠 

分 类 号：R61[医药卫生—外科学]